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Continuing Education Activity

Gout is one of the most common causes of chronic inflammatory arthritis in the United States, characterized by monosodium urate (MSU) monohydrate crystals deposition in the tissues. Gout was first recognized even before the common era. Hence it is arguably the most understood and manageable disease among other rheumatic diseases. This activity reviews the evaluation and management of gout and highlights the role of interprofessional team members in collaborating to provide well-coordinated care and enhance patient outcomes.


  • Identify the etiology of gout.
  • Explain the common physical exam findings associated with gout.
  • Describe the pathophysiology of gout arthritis.
  • Summarize interprofessional team strategies for improving care coordination and communication to advance gout and improve outcomes.


Gout is among the most prevalent etiologies of chronic inflammatory arthritis in the United States, characterized by monosodium urate (MSU) monohydrate crystals deposition in the tissues.[1][2] Gout was first recognized even before the common era, and hence it is the most understood and manageable disease among all rheumatic diseases.[3][4]

Gout is characterized biochemically by extracellular fluid urate saturation, which is reflected by hyperuricemia in the blood, with plasma or serum urate concentrations exceeding 6.8 mg/dL (approximately 400 micromol/L); this level is the approximate limit of urate solubility.[5] The clinical manifestations of gout may include:

  • Acute gout flare (recurrent flares of inflammatory arthritis)
  • Chronic gouty arthropathy
  • Accumulation of urate crystals in the form of tophaceous deposits
  • Uric acid nephrolithiasis
  • Chronic nephropathy


Risk Factors

Hyperuricemia is the leading cause of gout.[1][6] People with higher serum urate levels are not only at an elevated risk for gout flare-ups but will also have more frequent flare-ups over time. In a study of more than 2000 older adults with gout, those with levels more than 9 mg/dl were three times more likely to have a flare over the next 12 months than those with levels less than 6 mg/dl.[7]

Hyperuricemia is not the only risk factor for gout, and in fact, only a minority of these patients develop gout. Other factors implicated for gout and/or hyperuricemia include older age, male sex, obesity, a purine diet, alcohol, medications, comorbid diseases, and genetics. Offending medications include diuretics, low-dose aspirin, ethambutol, pyrazinamide, and cyclosporine. Genome-wide association studies (GWAS) have found several genes that are associated with gout. These include SLC2A9, ABCG2, SLC22A12, GCKR, and PDZK1[8]. Dietary sources that can contribute to hyperuricemia and gout include consumption of animal food such as seafood (e,g., shrimp, lobster), organs (e.g., liver, and kidney), and red meat (pork, beef). Some drinks like alcohol, sweetened beverages, sodas, and high-fructose corn syrup may also contribute to this disease.[1]

Risk factors of Hyperuricemia and Gout

                     Modifiable risk factors                                   Nonmodifiable risk factors              
Hypertension Age
Obesity Genetic variants
Hyperlipidemia Gender
Diabetes mellitus Ethnicity
 Cardiovascular disease  
 Medications altering urate balance  
 Chronic kidney disease  
 Dietary factors  

Causes of Hyperuricemia

Clinical disorders leading to urate and/ or purine overproduction Drug, diet, or toxin-induced urate and/or purine overproduction Inherited enzyme defects leading to purine overproduction (rare monogenic disorders)

Causes of hyperuricemia due to decreased uric acid clearance

Malignancies Cytotoxic drugs Glucose-6-phosphatase deficiency (glycogen storage disease, type I) Diabetic or starvation ketoacidosis
Hemolytic disorders Ethanol Hypoxanthine-guanine phosphoribosyltransferase deficiency Lactic acidosis
Myeloproliferative disorders Fructose Phosphoribosylpyrophosphate synthetase overactivity Chronic renal insufficiency of any form
Lymphoproliferative disorders Ethylamino-1,3,4-thiadiazole   Lead nephropathy (saturnine gout)
Tissue hypoxia Vitamin B12 deficiency   Hyperparathyroidism
Down syndrome Pancreatic extract   Sarcoidosis
Psoriasis Excessive dietary purine ingestion   Chronic beryllium disease
Glycogen storage diseases (types III, V, VII) 4-amino-5-imidazole carboxamide riboside   Hypothyroidism
Obesity     Preeclampsia
      Effective volume depletion (e.g., fluid losses, heart failure)


Every condition that causes alterations in extracellular urate concentration can trigger a flare-up. These conditions include stress (surgical procedure, recent trauma, or starvation), dietary factors (e.g., fatty food, beer, wine, and spirits), and drugs (e.g., aspirin, diuretics, or even allopurinol).


The prevalence of gout can vary by age, sex, and country of origin. In general, the prevalence of gout is 1 to 4%. Older age and male sex are two common risk factors noted globally. In western nations, the prevalence of gout in men (3 to 6%) is 2 to 6 fold higher than in women (1 to 2%). Prevalence increases with age but plateaus after 70 years of age. From 2007 to 2008, around 3.9% of U.S. adults received a diagnosis of gout.[9] Estimates of the gout prevalence in the United States range from less than three million to eight million or more individuals. The last of these estimates suggest gout prevalence in excess of three % of the adult American population.[10][11][12]

The adult serum urate levels of 5 to 6 mg/dL in men are usually reached at puberty, with a slight increase thereafter due to age alone.[13] The serum urate levels differ in women, whose serum urate concentrations average 1.0 to 1.5 mg/dL lower than men of corresponding ages.[14][15] The urate concentrations in women after menopause rise to levels comparable to those in adult men.[16] The gender differences in patterns of urate concentration tend to affect the clinical differences between women and men in the age of onset of gout.[17][18]


Hypertension, diabetes mellitus, hyperlipidemia, and metabolic syndrome are often associated with gout. Individuals with psoriasis have increased urate production and are prone to gout. On the other hand, patients with renal insufficiency have decreased urate excretion, resulting in gouty attacks. The prevalence of gout is also higher among individuals with chronic diseases such as hypertension, chronic kidney disease, diabetes mellitus, obesity, congestive heart failure, and myocardial infarction.[19]


Gout refers to a disease that occurs in response to the presence of MSU crystals in joints, soft tissues, and bones. It may result in a gout flare (acute arthritis), chronic gouty arthritis (chronic arthritis), or tophaceous gout (tophi)[20][21].

Following are a number of complex and interacting processes responsible for the pathophysiology of gout:

  • Genetic, metabolic, and other factors that result in hyperuricemia
  • Metabolic, physiologic, and other characteristics responsible for MSU crystal formation.
  • The soluble inflammatory, cellular, and innate immune processes and characteristics of MSU crystals themselves promote the acute inflammatory response.
  • Immune mechanisms that mediate the resolution of acute MSU crystal-induced acute inflammation
  • Chronic inflammatory processes and effects of immune cells and crystals on osteoblasts, chondrocytes, and osteoclasts contribute to cartilage attrition, bone erosion, joint injury, and formation of tophi. 


Hyperuricemia is the key factor for the development of gout as it can promote monosodium urate crystal nucleation and growth by reducing urate solubility. Uric acid in the blood comes from exogenous and endogenous purine breakdown, which gets excreted through the kidneys. Overproduction and/or underexcretion of uric acid is the foundation for rising serum uric acid levels.[6]


The solubility of MSU is determined by its concentration and factors that influence the nucleation and growth of crystals.[22] The solubility of MSU drops rapidly with decreasing temperature.[5]

Inflammatory Response

Inflammation starts when macrophages phagocytize monosodium urate crystals and trigger the formation and activation of cytosolic protein complexes (NLRP2 inflammasome).[23] These complexes subsequently recruit caspase-1, which activates pro-IL-1beta to IL-1beta.  IL-1beta plays an important role in the inflammatory response to gout.[3][23][24] It promotes vasodilatation, recruitment of monocytes and initiates and amplifies the inflammatory cascade. Further IL-1beta secretion can result in bone and cartilage breakdown. Other cytokines, such as TNF-1, IL-6, CXCL8, and COX-2, are also involved in the inflammatory response.[24]

Tophi are deposits of MSU crystals encompassing granulomatous inflammation. The tophus is a dynamic chronic inflammatory response to MSU crystal deposition that is complex and organized. Tophi are most often found in periarticular, articular, and subcutaneous areas, including cartilage, bone, joints, tendons, and skin, rich in proteoglycan. The tissue reaction to tophus is generally chronic inflammation and involves both adaptive and innate immunity. Few patients with tophaceous gout also present with chronic gouty arthritis (chronic synovitis). There is a close relationship between MSU crystal deposits and the development of cartilage and bone erosions.[25] Tophi contribute to joint damage and bone erosion in gout.[26] MSU crystal deposits are surrounded by osteoclast-like cells at the interface of the bone and a tophus.[27]


Monosodium urate crystal deposition, under polarizing light microscopy, is typically described as a rod or long needle-shaped crystals with negative birefringence.[28] Under light microscopy, tophi consist of several zones; the crystalline center, the surrounding corona zone, and then the fibrovascular zone. Multinucleated giant cells, histiocytes, and plasma cells are present in the corona zone.[29]

History and Physical

In a patient with a gout flare-up, the symptoms are often apparent. Gout flare is typically monoarticular, often occurring in the lower extremities.[30] The most commonly involved joint is the first metatarsophalangeal joint. In some cases, the talar, subtalar, ankle, and knee can also be involved. Although affliction of the joints mentioned above is common in gout, the physician should pay attention to other joints, specifically those joints with underlying osteoarthritis. Besides joints, other periarticular structures such as tendons and bursa may also be affected.[1] Gout can occur in axial joints such as sacroiliac joints and the spine, though much less common than peripheral involvement, leading to diagnostic confusion.[31][32]

Polyarticular gout flares are more likely to occur in patients with longstanding disease. Initial presentation of polyarticular gout is more frequent in patients in whom gout and hyperuricemia arise secondary to lymphoproliferative or myeloproliferative disorder or in organ transplant recipients receiving tacrolimus or cyclosporine.[33][34]

Patients usually present with acute onset of joint pain. Gout flares are more common at night and in the early morning period.[35] The pain is often sudden, waking the patient from sleep or may have developed gradually over a few hours before the presentation, with the maximum intensity of pain at 24 hours.[35] Signs of inflammation extend beyond the joint involved; this may give the impression of cellulitis or dactylitis (sausage digit) or may actually be due to tenosynovitis or arthritis in contiguous joints. The pain is usually severe and not responsive to the usual home remedies; even touching the joint can be excruciatingly painful. Gout flare-ups often incite local inflammation, which presents as erythematous, swollen, and a warm joint. Systemic features of joint inflammation may include fever, general malaise, and fatigue.[1]

The physical exam findings align with the patient's history. The affected joint is typically red, swollen, warm, and tender.[36] In patients with chronic gout, the flare-up may involve multiple joints. With the involvement of many joints, it can cause a systemic inflammatory response syndrome that may masquerade as sepsis.[37] Tophi, which are subcutaneous depositions of urate that form nodules, can also be found in patients with persistent hyperuricemia. Tophi typically occur in the joints, ears, finger pads, tendons, and bursae.[1]


Synovial Fluid Analysis

Monosodium urate crystal identification remains the gold standard for gout diagnosis. Gout flare is marked by the presence of MSU crystals in synovial fluid obtained from affected joints of bursas visualized by direct examination of a fluid sample using compensated polarized light microscopy. This technique may also identify uric acid crystals during the inter-critical period from previously affected tophaceous deposits and joints.[38] Synovial fluid during a gout flare-up usually is yellow in color and cloudier in appearance, and it contains crystals and white blood cells with neutrophil predominance. The synovial fluid will be more opaque in patients with septic arthritis with a yellow-green appearance. Under a microscopic examination, synovial fluid for septic arthritis will have a higher white blood cell count (over 50000/ml) than in gout and a positive gram stain. Additionally, cultures will be positive for bacteria and negative for crystals.

Synovial fluid or tophus aspiration analysis under polarizing microscopy reveals needle-shaped, negatively birefringent crystals.[1][3][39] Arthrocentesis is also necessary to confirm the diagnosis and rule out other septic arthritis, Lyme disease, or pseudogout (calcium pyrophosphate).[39]

Laboratory Study

The examination usually reveals elevations in the white blood cell count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) during a gout flare-up. Still, these features are non-specific and do not confirm the diagnosis.

During an acute gout flare-up, serum urate level may be high, normal, or low. The physician should repeat the serum urate level in patients with an uncertain gout diagnosis after the resolution of the flare-up. Hyperuricemia is helpful in the clinical diagnosis of gout in symptomatic patients, but hyperuricemia alone does not definitively confirm the diagnosis. Asymptomatic hyperuricemia is not uncommon in the general population. Persistently low serum urate concentrations make the diagnosis of gout less likely.[3] In patients suspected of gout based on clinical features, elevated serum urate level (>6.8 mg/dL) can support the diagnosis but is neither diagnostic nor required to establish the diagnosis. The most accurate time for assessing serum urate level to establish a baseline value is two weeks or more after a gout flare completely subsides.

Urinary fractional excretion of uric acid can be measured, especially in young populations with a non-specific cause of hyperuricemia. It will help differentiate between overproduction or under excretion of uric acid and can act as a guide for therapy.


Although not routinely used, ultrasonography and dual-energy CT (DECT) can assist in diagnosing gout. Monosodium urate deposition will be apparent on ultrasound as a hyperechoic enhancement over the cartilage, also known as a double contour sign. DECT can identify urate due to the beam attenuation after exposure to two different X-ray spectra.[1][3]

Treatment / Management

The treatment of gout is based on the goals of treatment. During acute flares, the goal is solely to reduce the inflammation and symptoms. Long term goal is to reduce serum urate levels to achieve suppression of flare-ups and regression of tophi.[3]

General Principles of Therapy

  • The earlier the treatment is introduced for a gout flare, the rapid and complete resolution of symptoms occurs.[40]
  • The duration of gout flare therapy ranges from a few days to several weeks, depending on the timing of treatment initiation.[41]
  • Anti-inflammatory gout flare prophylaxis should generally be continued during the early months of urate-lowering therapy.[42]
  • For patients receiving urate-lowering therapy at the time of gout flare, the urate-lowering medication should be continued without interruption as there is no benefit to temporary discontinuation.
  • Tophus is an indication to initiate long-term urate-lowering therapy either during or following the resolution of a gout flare to reverse or prevent joint damage and chronic gouty arthritis.

Acute Gout Flare

Management of acute flares aims at decreasing the inflammation and the resulting pain. The physician should start the treatment within the first 24 hours of onset to reduce the severity and duration of the flare-up.[6]

Non-pharmacological management such as rest with topical application of ice packs can combine with medications that reduce inflammation.[43] First-line treatment for gout flares are (nonsteroidal anti-inflammatory drug) NSAIDs, colchicine, or systemic glucocorticoids.[44] The length of the treatments should be at least 7 to 10 days to prevent rebound flare-ups.[45]

There is no data to favoring one NSAID over the other. High-dose, fast-acting NSAIDs such as naproxen or diclofenac are options, and indomethacin is not preferable due to its toxicity profile.[6]

Patients experiencing a gout flare and able to take oral medications, suggested first-line options are oral glucocorticoids, NSAIDs, and colchicine.

Oral Glucocorticoids

  • Glucocorticoids are recommended in gout patients but have contraindications to NSAIDs and/or colchicine.
  • These agents are also drugs of choice for patients with renal insufficiency.
  • Glucocorticoids can be administered intra-articularly for a monoarticular gout flare-up or orally for polyarticular flare-ups.
  • The initial dose for gout flare is 30 to 40 mg of prednisolone or prednisone once daily or given in a divided twice-daily dose until flare resolution begins, and then taper the dose of glucocorticoids over the next 7 to 10 days.
  • The efficacy of Glucocorticoids is similar or superior to other agents and has no greater risk of adverse effects in most patients.[46]
  • In patients with concomitant or suspected infections, uncontrolled diabetes mellitus, prior glucocorticoid intolerance, and in post-operative status, glucocorticoids may heighten the risk of impaired wound healing.
  • In patients with an unclear diagnosis of an acute gout flare, arthrocentesis and synovial fluid analysis should be performed, and oral and intra-articular glucocorticoids must be avoided until the results are available; instead, initiation of other agents like NSAID or colchicine be considered.
  • Frequent adverse effects of moderate- to high-dose, short-term glucocorticoid use include hyperglycemia, fluid retention, increased blood pressure, and mood changes. Repeated and frequent courses of glucocorticoids should be avoided to limit adverse effects.
  • Extended tapering doses of glucocorticoids up to 14 or even 21 days is advised in patients with rebound flares, shortened inter-critical periods, and not receiving anti-inflammatory prophylaxis.

Intraarticular Glucocorticoids

  • Joint fluid aspiration and intraarticular glucocorticoid injection are suggested for patients with monoarticular gout flare with a low likelihood of infection and who cannot tolerate oral medications.
  • Triamcinolone acetonide (10 mg for a small joint, 30 mg for a medium joint like ankle, elbow, or wrist, and 40 mg for a large joint like knee) or equivalent doses of methylprednisolone acetate are used.

Parenteral Glucocorticoids

  • Intravenous or intramuscular glucocorticoids are suggested in patients who are not candidates for intraarticular glucocorticoid injection or cannot take oral medications.
  • A typical dose of methylprednisolone is 20 mg intravenously twice daily, with stepwise reduction and rapid transition to oral prednisone when improvement begins.
  • Triamcinolone acetate (40 to 60 mg or equivalent dose of methylprednisolone given intramuscularly) has also been reported to be effective.[47][48] However, the dose may need to be repeated at intervals of 48 hours to achieve resolution of the flare.
  • Adrenocorticotropic hormone (ACTH) has also been described as efficacious for treating gout flare, but limited availability and cost restrict its use.


  • NSAIDs are most effective when therapy is initiated within 48 hours of the onset of gout symptoms.
  • NSAIDs are recommended in patients without cardiovascular, renal, or active gastrointestinal disease and younger patients.
  • A potent oral NSAID, such as indomethacin (50 mg three times daily) or naproxen (500 mg twice daily), is a reasonable alternative to glucocorticoids.
  • Other NSAIDs representing possible include meloxicam (15 mg daily), ibuprofen (800 mg three times daily), diclofenac (50 mg two to three times daily, and celecoxib (200 mg twice daily). The dose of these medications may be reduced after improvement in the symptoms.
  • Typically NSAID treatment for gout flare lasts for five to seven days.
  • Contraindications for the use of NSAIDs include active duodenal or gastric ulcer, cardiovascular disease (uncontrolled hypertension or heart failure), NSAID allergy, chronic kidney disease with creatinine clearance (CrCl) of less than 60 ml/minute per 1.73 square meters.
  • Aspirin is not used to treat gout flare due to the paradoxical effects of salicylic acid on serum urate levels.[49][50] This results from uricosuria at higher doses and renal uric acid retention at low doses (less than 2 to 3 g/day).[51][52]


  • Colchicine is comparably effective to other agents if taken within 24 hours of gout flare onset. Colchicine has been shown to reduce pain by over 50% in a randomized control trial at 24 hours compared to a placebo.
  • The total dose of colchicine should not exceed 1.8 mg on day 1 (either 1.2 mg for the first dose followed by 0.6 mg an hour later [US Food and Drug Administration (FDA) approved dose] or 0.6 mg three times on the first day.[53] On subsequent days, colchicine should be taken once or twice daily until the resolution of a gout flare.[54]
  • A reduced dose of colchicine may be required for patients with diminished hepatic or renal function or potential drug interactions.
  • High-dose colchicine regimens should not be encouraged due to unacceptably high toxicity.
  • Patients taking colchicine who are also on other medications that affect cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp) may need to modify or stop their medication regimen due to increased risk of colchicine toxicity. The adverse effects of colchicine comprise gastrointestinal symptoms (nausea and diarrhea), myotoxicity, and myelosuppression (leukopenia, thrombocytopenia, and aplastic anemia).[55]
  • The frequent adverse effects of colchicine are abdominal cramping and diarrhea.[53][56]
  • Colchicine dosing adjustments for certain high-risk groups of patients should follow the guidelines provided in the manufacturer's FDA-approved information. Usually, no more than 0.3 mg dose is administered on the day of a gout flare, and the dose is not repeated for at least three to seven days or more in such patients. Following are the high-risk groups: 
    • Patients taking colchicine prophylaxis within the past 14 days, with normal hepatic and renal function, who have taken a medication that inhibits P-gp and strong CYP3A4 inhibitor within the last 14 days
    • Patients taking colchicine prophylaxis within the past 14 days, with any hepatic and renal impairment, who have taken a medication that is a moderate CYP3A4 inhibitor within the last 14 days
    • Patients with advanced hepatic or renal impairment (Child-Pugh C cirrhosis or equivalent CrCl of <30 mL/minute) regardless of recent colchicine use.
    • Intravenous colchicine is strongly advised against due to serious adverse effects, including death.

Non-acute Flares


The clinician should not start urate-lowering therapy (ULT) in patients with asymptomatic hyperuricemia or gout with rare attacks (1 flare/year). The American College of Rheumatology (ACR) 2012, Guidelines for starting ULT include the following:

  1. Frequent or disabling gout flares (greater than or equal to two per year).
  2. Gout with chronic kidney disease (stage 3 or higher).
  3. Tophus diagnosis on physical examination or imaging.
  4. Past urolithiasis.

Urate-lowering therapy is started at a low dose to monitor the side effects and response to treatment. Titration of the dose is every 2 to 6 weeks to achieve serum urate levels of less than 6 mg/dl or 5 mg/dl in those patients with tophi.[43]

During the initiation of ULT, there is an increased risk of gout flare-ups, so colchicine prophylaxis is recommended for three months after achieving serum urate goal in the patients without tophi or six months with tophi in order to reduce the flare-up risk.[57]

ULT can categorize into three classes (based on the mechanisms).

Xanthine oxidase inhibitors (XOI) - XOI works by inhibiting uric acid synthesis. This class includes allopurinol and febuxostat. Allopurinol is the recommended first-line pharmacologic ULT in gout.[43] The physician should monitor liver enzymes, renal, and blood count regularly. Adverse effects from allopurinol can range from skin rashes to life-threatening severe allopurinol hypersensitivity (especially in HLA-B*5801 positive patients).[1]


  • The initial allopurinol dose is 100 mg daily in patients with CrCl greater than 60 mL/minute.
  • A starting dose of allopurinol of <1.5 mg per mL/minute of estimated glomerular filtration rate (eGFR) is advised in patients with stage 3 or greater chronic kidney disease.
  • Adverse effects of allopurinol - may precipitate gout flares, rash, leukopenia, thrombocytopenia, diarrhea, and severe cutaneous adverse reactions.
  • (DRESS) syndrome - Drug reaction with eosinophilia and systemic symptoms is a potentially life-threatening reaction to allopurinol.
  • Allopurinol can potentiate the cytolytic and immunosuppressive effects of azathioprine and 6-mercaptopurine (6-MP), which are in part metabolized by xanthine oxidase.[58] Hence, allopurinol should be avoided in patients treated with these agents.[59]


  • Febuxostat received FDA approval to treat gout patients with hyperuricemia at daily doses of 40 and 80 mg.
  • Cardiovascular and hepatic abnormalities may be more common with febuxostat compared with allopurinol.
  • Patients taking azathioprine, 6-MP, and theophylline are considered contraindications to the use of febuxostat.

Uricosuric drugs - The uricosuric agents work by increasing renal urate clearance.[1] Patients with low or normal urinary uric acid excretion in the presence of hyperuricemia are potential candidates for uricosuric therapy. Drugs in this class include probenecid and lesinurad (withdrawn from the market in the United States). These agents are ineffective as monotherapy in patients with low creatinine clearance (less than 30 ml/minute) and contraindicated with patients with a history of nephrolithiasis.[60] Probenecid is the only agent approved for use as a monotherapy. Probenecid is initiated at a dose of 250 mg twice daily, and dose increments are titrated according to the serum urate concentration level. The dose is typically increased every several weeks to a usual maintenance dose of 500 to 1000 mg (taken 2 to 3 three times daily), aiming for the target urate levels of <6 mg/dL (<357 micromol/L). The major side effects of uricosuric drugs are the precipitation of a gout flare, uric acid urolithiasis, gastrointestinal intolerance, and rash.

Uricase (urate oxidase) - Uricase is reserved only for patients with refractory gout. Uricase converts uric acid into soluble allantoin. Pegloticase (a pegylated recombinant form of uricase) is a potent agent that rapidly reduces serum urate levels. Patients have to discontinue urate-lowering therapy while starting this medication because they may develop antibodies against uricase. Pegloticase is administered as intravenous infusions every two weeks, and before each infusion, serum urate levels should be monitored to confirm urate-lowering efficacy. For at least the first six months of treatment, all patients treated with pegloticase should receive gout flare prophylaxis. In patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, pegloticase is contraindicated. Another agent Rasburicase (non-pegylated recombinant uricase), has not been approved by FDA for use in gout. It is used to prevent acute uric acid nephropathy due to tumor lysis syndrome in patients with high-risk leukemia and lymphoma. 


Patients with gout are encouraged to modify their lifestyles to prevent future attacks.

Diet recommendations include reducing alcohol consumption, limiting purine-rich foods (meat, seafood, high fructose corn syrup, and sweetened soft drinks), and substituting low-fat or non-fat dairy products for their higher fat content counterparts. Weight loss and adequate hydration will also help reduce gout flare-up frequency.

Differential Diagnosis

Gout Flare

  • Calcium pyrophosphate crystal deposition disease
  • Basic calcium phosphate crystal disease
  • Septic arthritis
  • Osteoarthritis
  • Psoriatic arthritis
  • Cellulitis
  • Trauma

Tophaceous Gout

  • Dactilytis
  • Rheumatoid arthritis
  • Osteomyelitis


The prognosis of gout depends on the comorbidity of each individual. Mortality is higher in individuals with cardiovascular comorbidity. When gout receives proper treatment, most patients will live a normal life with mild sequelae. Patients whose symptoms appear earlier in life will usually have a more severe disease at presentation. For those who do not modify their lifestyle, recurrent flare-ups are common.


Tophi, joint deformity, osteoarthritis, bone loss.

Urate nephropathy and nephrolithiasis.

Gout might also cause ocular complications, such as conjunctivitis, uveitis, or scleritis from the urate crystal precipitation.[61]

Deterrence and Patient Education

Lifestyle modification and strategies to reduce the risk of gout flares and progression of gout:

  • Lifestyle changes are encouraged in gout patients, including weight loss, limiting alcohol intake, and avoiding certain foods. These changes will complement medical therapy but often are not enough by themselves to combat or reverse gout.
  • Weight gain and increased adiposity are risk factors for gout, while in overweight patients with established gout, weight loss likely benefits in reducing serum urate and gout symptoms.[62][63]
  • The diet composition optimum for gout is likely to be one with adequate protein intake, especially from plant sources and low-fat dairy sources, with reduced intake from animal sources of purine such as shellfish or red meat; decreased saturated fat; and replacement of simple sugars with complex carbohydrates.
  • Avoid or minimize the frequency of sugar-sweetened juices and alcohol-containing beverages or beverages containing high-fructose corn syrup.

Pearls and Other Issues

Interleukin (IL) 1 is an important mediator of inflammation in gout and a potential target for therapy in gout flares.[64] For patients with multiple medical comorbidities and those on anticoagulation, a short-acting (IL) 1 inhibitor, such as anakinra, can be used to treat gout flare as an alternative to the first-line therapies.

Enhancing Healthcare Team Outcomes

Most patients with gout have other comorbidities. The prevalence of gout is higher among individuals with chronic diseases such as hypertension, chronic kidney disease, diabetes, obesity, congestive heart failure, and myocardial infarction.[19]

Gout treatment requires the collaboration of an entire interprofessional healthcare team approach. The physician (MD, DO, NP, PA) must promptly identify the pathology and rule out differentials. Some cases may require a rheumatology consult. The pharmacological approaches to gout require considering these comorbidities and monitoring their response to treatment. The pharmacist and nurse both must educate the patient on medication compliance. Also, the pharmacist should assist the team by performing medication reconciliation, verifying appropriate dosing, and consulting on agent selection in the event of initial treatment failure. The dietitian should urge the patient to abstain from alcohol, avoid meat-containing foods, and maintain healthy body weight. The role of specialists, primary care physicians, nurses, nurse practitioners, and dieticians are all critical in reducing gout morbidities. The medical team should coordinate the patient's education on lifestyle modification, which can contribute to reducing the risk and frequency of gout flare-ups.  

All healthcare providers, including primary care and nurse practitioners, should identify classic gout symptoms and have a low threshold for referring the patients for an arthrocentesis if they are uncertain of the diagnosis. Then, working with the interprofessional team as outlined above, direct the treatment as needed and interact with the interprofessional team to drive outcomes. [Level 5]

Referral to a specialist/rheumatologist should be a consideration in the following patients with joint pain: 

  • Unclear etiology with hyperuricemia
  • Unclear etiology with normal serum urate level
  • Patients with renal impairment
  • Failed trial of xanthine oxidase inhibitor treatment
  • Multiple side effects from the medications
  • Refractory gout[43]

Only through an interprofessional team approach with close communication can the morbidity of gout be lowered.

(Click Image to Enlarge)
Hand Radiograph Gout
Hand Radiograph Gout
Contributed by Scott Dulebohn, MD

(Click Image to Enlarge)
Gout, [SATA]
Gout, [SATA]
Contributed by Steve Bhmji, MS, MD, PhD

(Click Image to Enlarge)
Gout in the Ear
Gout in the Ear
Image courtesy S Bhimji MD

(Click Image to Enlarge)
Acute gout attack
Acute gout attack
Image courtesy O.Chaigasame

(Click Image to Enlarge)
Gout Tophi
Gout Tophi
Contributed by Dr. Shyam Verma, MBBS, DVD, FRCP, FAAD, Vadodara, India
Article Details

Article Author

Ardy Fenando

Article Author

Manjeera Rednam

Article Author

Rahul Gujarathi

Article Editor:

Jason Widrich


12/7/2021 9:04:04 PM

PubMed Link:




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